Chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) are currently tested for the Philadelphia (Ph') translocation on the basis of cytogenetic methods. The objective of this proposal is the development of a simpler, cost effective and rapid immunological test for this purpose. Preliminary studies suggest that as a consequence of its translocation from chromosome 9 to 22 in CML, the c-abl oncogene is expressed at the carboxy terminus of a chimeric polyprotein. The amino terminal domain of this protein appears to be encoded by the bcr region of chromosome 22. In Phase I this model will be directly tested by molecularly cloning cDNAs corresponding to the human c-abl oncogene. 5' and 3' c-abl probes will be prepared and, by analysis of appropriate somatic cell hybrids, used to establish whether the Ph' breakpoint on chromosome 9 maps within the c-abl genetic locus. Phase II research will involve a determination of the nucleic acid sequence of the c-abl locus and preparation of synthetic peptides. In addition, c-abl cDNA sequences will be inserted into appropriate expression vectors. Monoclonal antibodies with specificity for the c-abl protein in combination with antibodies specific for the bcr region of chromosome 22 will be used for the development of an immunologic test for diagnosis of the Ph' translocation.